Meta-analysis of coagulation disbalances in COVID-19: 41 studies and 17601 patients

Introduction. Coagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the early hemostatic parameters in retrospective studies in association with severity of infection. Methods. Ovid, PubMed, Web of Sciences, and Google Scholar were searched for research articles that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference with 95% CI for each of five coagulation parameters (D-dimers, fibrinogen, prothrombin time, platelets count, activated partial thromboplastin time). Two authors independently extracted data and assessed study quality. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger test by linear regression. Results. Overall, 41 original studies (17601 patients) on SARS-CoV2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group (SMD 0.6985 with 95%CI [0.5155; 0.8815]); SMD 0.661with 95%CI [0.3387; 0.9833]; SMD 0.2683 with 95%CI [0.1357; 0.4009]; SMD 0.284 with 95%CI [0.1472; 0.4208]). In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 (SMD -0.1684 with 95%CI [-0.2826; -0.0542]). Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias. Conclusions. The standard coagulation laboratory parameters with exception of platelets counts are significantly elevated in patients with severe COVID-19. However, fibrinolysis shutdown requires evaluation outside conventional coagulation tests and analysis of additional specific markers related to clotting formation and PLT characteristics. We hypothesize that a proportion and parameters of immature reticulated platelets may serve as additional biomarkers for prediction of adverse events.

Gastrointestinal Bleeding in COVID-19 Patients: A Systematic Review with Meta-Analysis

The novel coronavirus disease 2019 (COVID-19) has been reported to affect the gastrointestinal system with a variety of symptoms, including bleeding. The prevalence of bleeding in these patients remains unclear. The aim of this meta-analysis is to estimate the rate of gastrointestinal bleeding in COVID-19 patients and its association with mortality. MEDLINE and Embase were searched through December 20, 2020. Studies reporting COVID-19 patients with and without gastrointestinal bleeding were included. Estimated prevalence with 95% confidence intervals (CI) was pooled; heterogeneity was expressed as I2. Metaregression analysis was performed to assess the impact of confounding covariates. Ten studies met the inclusion criteria and were included in the analysis. A total of 91887 COVID-19 patients were considered, of whom 534 reported gastrointestinal bleeding (0.6%) [409 (76.6%) upper and 121 (22.7%) lower gastrointestinal bleeding (UGIB and LGIB, resp.)]. The overall pooled gastrointestinal bleeding rate was 5% [95% CI 2–8], with high heterogeneity (I2 99.2%); “small study effect” was observed using the Egger test ( p = 0.049 ). After removing two outlier studies, the pooled bleeding rate was 2% [95% CI 0–4], with high heterogeneity (I2 99.2%), and no “small study effect” ( p = 0.257 ). The pooled UGIB rate was 1% (95% CI 0–3, I2 98.6%, p = 0.214 ), whereas the pooled LGIB rate was 1% (95% CI 0–2, I2 64.7%, p = 0.919 ). Metaregression analysis showed that overall estimates on gastrointestinal bleeding were affected by studies reporting different sources of bleeding. No significant association between gastrointestinal bleeding and mortality was found. In this meta-analysis of published studies, individuals with COVID-19 were found to be at risk for gastrointestinal bleeding, especially upper gastrointestinal bleeding.

Dental Health Inequalities among Indigenous Populations: A Systematic Review and Meta-Analysis

The aim of this systematic review and meta-analysis was to document the disparity in dental caries experiences among indigenous and nonindigenous populations globally by measuring dental caries prevalence and severity. An electronic database (MEDLINE) was initially searched using relevant keywords. This was followed by use of the search string in the following electronic databases: Scopus, EBSCOhost, Cochrane, and Open Grey. Two independent reviewers conducted the study search and screening, quality assessment, and data extraction, which was facilitated using JBI SUMARI software. The primary outcome was the decayed missing filled teeth (DMFT) score and dental caries prevalence. Subgroup analysis was done by country of publication to identify causes of heterogeneity. Forest plots were used with the standardized mean difference (SMD) and publication bias was assessed using the Egger test with funnel plot construction. For the final review, 43 articles were selected and 34 were meta-analyzed. The pooled mean DMFT for both the permanent dentition (SMD = 0.26; 95% CI 0.13–0.39) and deciduous dentition (SMD = 0.67; 95% CI 0.47–0.87) was higher for the Indigenous population than for the general population. Indigenous populations experienced more decayed teeth (SMD = 0.44; 95% CI 0.25–0.62), a slightly higher number of missing teeth (SMD = 0.11< 95% CI –0.05 to 0.26), and lesser filled teeth (SMD = –0.04; 95% CI –0.20 to 0.13) than their nonindigenous counterparts. The prevalence of dental caries (SMD = 0.27; 95% CI 0.13–0.41) was higher among indigenous people. Globally, indigenous populations have a higher caries prevalence and severity than nonindigenous populations. The factors which have led to such inequities need to be examined.

POS0873 IMPROVEMENT IN MODIFIED RODNAN SKIN SCORE (MRSS) IN SYSTEMIC SCLEROSIS PATIENTS TREATED WITH RITUXIMAB: A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE SCIENTIFIC LITERATURE

Background:Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissue characterized by vascular disease and fibrosis in different organs and systems such as lung and skin (1). Recently, several case reports and small series of patients reported on the efficacy of rituximab in SSc, showing a possible improvement in skin and lung affectations (2). However, registered clinical trials are lacking to determine factors associated with response, maintenance regimen, and long-term efficacy of rituximab in SSc.Objectives:To analyze the efficacy of Rituximab in the treatment of skin fibrosis using the changes of the modified Rodnan Skin Score (mRSS) of patients diagnosed with systemic sclerosis from the data published in Registered Clinical Trials (RCTs) in the scientific literature.Methods:We perform a systematic review and a meta-analysis using the main electronic databases to locate all the articles available so far: Medline, Embase, Cochrane Library and Web of science and ACR and EULAR abstracts congress were extracted to assess efficacy outcomes. That efficacy was measured based on the variation of mRSS at 12, 24 and 48 weeks for patients treated with Rituximab versus patients treated with another drug or placebo.Results:3 RCTs contained data regarding mRSS at week 12 of treatment with Rituximab. The estimated SMD was -1.071 (95% CI -1.608, -0.535 [p <0.001]) with a non-significant P value in the Egger Test (P = 0.703) and non-significant heterogeneity through I2 (I2 = 0.00%).9 studies contained data regarding mRSS at week 24 of treatment with Rituximab. The estimated SMD was -1.743 (CI95% -2.622, -0.864 [p <0.001], see image below) with a non-significant P value in the Egger Test (P = 0.072) and significant heterogeneity through I2 (I2 = 86.6%). Meta-regression analysis could not be performed to assess such heterogeneity, due to the lack of comparable data.8 RCTs contained data regarding mRSS at week 48 of Rituximab treatment. The estimated SMD was -1.327 (CI95% -2.018, -0.636 [p <0.001]) with a significant P value in the Egger Test (P = 0.018), estimating that there may be publication bias in the studies analyzed and significant heterogeneity by I2 (I2 = 85.2%). Meta-regression analysis could not be performed to assess such heterogeneity, due to the lack of comparable data.Conclusion:Our meta-analysis shows that Rituximab treatment in patients affected with systemic sclerosis shows efficacy in the treatment of cutaneous fibrosis measured by the mRSS, turning this molecule into a potential drug to add to the therapeutic armamentarium of systemic sclerosis. However, more studies are necessary to try to elucidate whether this change is powerful enough to become the new gold standard for the treatment of systemic sclerosis skin involvement.References:[1]Stern EP, Denton CP. The pathogenesis of systemic sclerosis. Rheum Dis Clin North Am 2015;41:367–82. https://doi.org/10.1016/j.rdc.2015.04.002.[2]Thiebaut M, Launay D, Rivière S, et al. Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review. Autoimmun Rev. 2018;17(6):582-587. https://doi:10.1016/j.autrev.2017.12.010.Disclosure of Interests:None declared

Prevalence of cystic echinococcosis in slaughtered livestock in Iran: a systematic review and meta-analysis

Background Hydatidosis is a zoonotic disease and has a great general and economic health importance in both developed and developing countries. Therefore, this systematic and meta-analytic study was conducted to determine the prevalence of cystic echinococcosis in slaughtered livestock in Iran. Methods The present study was conducted as a systematic review and meta-analysis. The SID & Magiran, MEDLINE (PubMed), ScienceDirect, Scopus, and Google Scholar databases were searched with a view to selecting relevant research works. As a result, 31 articles published from April 1970 to April 2020 were selected. The heterogeneity of the studies was assessed using the I2 index. Data analysis was conducted within the Comprehensive Meta-Analysis software (CMA) v.3.0 (Biostat, Englewood, NJ, USA) and Arc map (ArcGIS 10.3) software. Results The heterogeneity of the studies was evaluated using the I2 test which value was 99% showing a high heterogeneity in the studies. The results of publication bias in studies were evaluated by the Egger test, which were not statistically significant (P = 0.144). The overall prevalence of cystic echinococcosis in slaughtered livestock in Iran is 13.9% (95%CI: 10.7–17.7%). The results of the meta-regression analysis indicate the increasing trend of the hydatid cyst prevalence with the increase of sample size and publication year (P < 0.05). Conclusion According to the results of this study and the relatively high prevalence of cystic echinococcosis in slaughtered livestock in Iran, health policy makers should make effective decisions in this regard, and implement careful inspections and interventions by experts and health authorities.

P74 Long-term Survival After Minimally Invasive Resection versus Open Pancreaticoduodenectomy for Pancreatic Cancers: A Systematic Review and Meta-analysis

Introduction It remains unclear whether minimally invasive pancreaticoduodenectomy (MIPD) and open pancreaticoduodenectomy (OPD) influences long-term survival in periampullary cancers. This review aims evaluate long-term survival between MIPD and OPD for periampullary cancers. Methods A systematic review was performed to identify studies comparing long-term survival after MIPD and OPD. The I2 test was used to test for statistical heterogeneity and publication bias using Egger test. Random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year survival, and disease-specific 5-year and 3-year survival. Meta-regression was performed for the 5- year and 3-year survival outcomes with adjustment for study (region, design, case matching), hospital (centre volume), patient (ASA grade, gender, age), and tumor (stage, neoadjuvant therapy, subtype (i.e. ampullary, distal bile duct, duodenal, pancreatic)). Sensitivity analyses performed on studies including pancreatic ductal adenocarcinoma (PDAC) only. Results The review identified 31 relevant studies. Among all 58,622 patients, 8716 (14.9%) underwent MIPD and 49,875 (85.1%) underwent OPD. Pooled analysis revealed similar 5-year overall survival after MIPD compared with OPD (HR: 0.78, 95% CI 0.50–1.22, p = 0.2). Meta-regression indicated case matching, and ASA Grade II and III as confounding covariates. The statistical heterogeneity was limited (I2 = 12, c2 = 0.26) and the funnel plot was symmetrical both according to visual and statistical testing (Egger test = 0.32). Sensitivity subset analyses for PDAC demonstrated similar 5-year overall survival after MIPD compared with OPD (HR 0.69, 95% CI: 0.32–1.50, p = 0.3). Conclusion Long-term survival after MIPD is similar to OPD. Thus, MIPD can be recommended as a standard surgical approach for periampullary cancers.

Association between convalescent plasma and the risk of mortality among patients with COVID-19: a meta-analysis

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Embase, PubMed, Web of Science, Cochrane and MedRix were searched for potentially relevant articles. All included papers were assessed for the quality using modified jadad scale and Newcaste-ottawa scale for randomized controlled trial (RCT) and non – RCT, respectively. We used a Q test and Egger test to assess the heterogeneity and publication bias among studies, respectively. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 12 papers consisting of three cross-sectional studies, one prospective study, five retrospective studies, and two RCT studies were included in our analysis. Of them, a total of 1,937 patients treated with CCP and 3,405 patients without CCP were involved.. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without the CCP had a 1.32 times higher risk of mortality than those treated with the CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, reduces the mortality rate among COVID-19 patients.

Systematic Review and Meta-analysis of Carbapenem Resistance of Acinetobacter baumannii in Iran

Introduction: The prevalence of carbapenem resistance in Acinetobacter baumannii has been increasing worldwide, and therapeutic options are extremely limited. We performed a systematic review to evaluate the phenotypic and genotypic carbapenem resistance in A.baumannii reported in Iran. Methods: We systematically searched Pub Med, Web of Science Direct, and Google scholar databases to identify studies addressing the carbapenem resistance of A. baumannii. The selected papers were published between 2005 and 2016, but the sample collection period was between 2002 and 2016. To estimate the prevalence, the Der Simonian and Laird randomized models, a 95% confidence interval, was used. For the heterogeneity check, I2 test was used. The Egger test was used to check the propagation bias. Results: Analysis of data indicates that there was an increase in resistance to carbapenems from 4.5% in 2005 to a 100% prevalence rate in 2016 (65.4 (95% CI: 58.8 – 71.6). Conclusion: According to the results of this study, the rate of resistance to carbapenem in A.baumannii has been increasing in Iran. The presence of carbapenem-resistant isolates is a major concern, because carbapenem is the main drug used against Multi Drug Resistant (MDR) isolates.

377. Diabetes as a prognostic factor for mortality in Coronavirus Disease 19 (COVID-19): a systematic review and meta-analysis comprising 18,506 patients

Background Diabetes Mellitus is one of the leading causes of morbidity and mortality in the world. Infectious diseases are more common and associated with worse outcomes among diabetics. Diabetes is considered a predictor of morbidity in patients with COVID-19. Methods Medline, Embase, Google Scholar, and medRxiv were systematically reviewed up to May 10th, 2020 for observational studies on diabetic adult populations hospitalized for COVID-19 and that assessed possible correlation between diabetes and mortality. A meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Heterogeneity among trials for each outcome was assessed with the I-squared test. Values &lt; 25% indicated low, 25 to 70% moderate, and &gt; 70% high heterogeneity. Egger test and funnel plots were used to assess for publication bias. Results Fourteen observational studies (12 retrospective and 2 prospective) met the prespecified criteria for inclusion in the analysis, including 18,506 patients (43% women): 3,713 diabetics (DM group) and 14,793 non-diabetics (no-DM group). The mean or median age was above 60 years in 12 studies. DM group had a higher risk of death compared to the no-DM group, heterogeneity was significant (OR: 1.65; 95% CI: 1.35–1.96; I2 77.4%). Sensitivity analysis for US studies only also revealed a higher chance of death among the DM group (OR: 1.34; 95% CI: 1.04–1.85; I2 73.7%). Conclusion In conclusion, death was 65% more likely among diabetic inpatients compared to non-diabetics. Further studies are needed to assess whether this association is independent or not, and to investigate to role of glucose control prior or during the disease. Disclosures All Authors: No reported disclosures

Oral vancomycin prophylaxis for the prevention of Clostridium difficile infection: A systematic review and meta-analysis

Objective:Recently, oral vancomycin prophylaxis (OVP) has been suggested for the prevention of Clostridium difficile infection (CDI). We conducted a systematic review and meta-analysis to investigate the efficacy and safety of this approach.Design:Systematic review and meta-analysis.Methods:We conducted a computerized search of MEDLINE, EMBASE, and Cochrane databases from inception to March 2019 for publications investigating OVP for CDI prevention. Results were screened for eligibility. Relevant data were extracted and analyzed. Publication bias was assessed using the Egger test.Results:Ultimately, 8 retrospective studies and 1 prospective study examining 2174 patients, published between 2016 and 2019 were included in the review. OVP was associated with decreased CDI (odds ratio, 0.263; 95% confidence interval, 0.13–0.52) with considerable heterogeneity (I2 = 61%). Meta-regression showed that total daily dose of OVP correlated with CDI, explaining 100% of heterogeneity between studies. Furthermore, 3 studies evaluated the risk of vancomycin-resistant enterococci (VRE) infection after OVP and found no significant increase.Conclusion:Our results suggest that OVP might decrease CDI rates in at-risk populations, although this conclusion should be interpreted with caution. Higher daily doses of OVP might increase CDI. Although the use of OVP in high-risk patients may reduce CDI, this suggestion has yet to be validated by prospective blinded randomized controlled trials.